A Phase 1/2 Open-Label Study Evaluating the Safety and Efficacy of ST-067 in Combination With CD19-Directed CAR T-Cell Therapy in Patients With Relapsed/Refractory (R/R) Large B-Cell Lymphoma (LBCL)
Summary
This phase I/II trial tests the safety, side effects, and best dose/regimen of ST-067 in combination with CD19-directed chimeric antigen receptor (CAR) T-cell therapy (liso-cel) and how well it works in treating patients with large B-cell lymphoma (LBCL) that has come back after a period of improvement (recurrent) or LBCL that has not responded to previous treatment (refractory). ST-067 is an engineered variant of the human cytokine interleukin-18 that may help the immune system kill cancer cells. Lisocabtagene maraleucel (liso-cel) is an autologous CAR T-cell therapy prepared using the person's own immune system (a group of cells, tissues, and organs that protect the body from attack by bacteria, viruses, and cancer cells) to fight the cancer. Giving ST-067 in combination with liso-cel may better treat patients with relapsed/refractory LBCL.
Detailed description
OUTLINE: This is a phase I, dose-escalation study of ST-067 followed by a phase II study. Patients undergo leukapheresis and lymphodepleting chemotherapy between days -5 to -3 prior to treatment and receive liso-cel intravenously (IV) on day 0. Patients then receive ST-067 subcutaneously (SC) weekly on days 14, 21, and 28 or days 10, 17, and 24. Patients may continue to receive maintenance ST-067 SC at day 35 once weekly. Treatment continues for up to 8 doses in the absence of disease progression or unacceptable toxicity. Patients undergo x-ray imaging, and echocardiography (ECHO) or multigated acquisition scan (MUGA) during screening. Patients also undergo computed tomography (CT) and/or positron emission tomography (PET) as well as lumbar puncture for cerebral spinal fluid (CSF) collection and bone marrow aspiration and biopsy as clinically indicated during screening and follow-up. Patients undergo blood sample collection throughout the study. After completion of study treatment, patients are followed up at 3, 6, 9, and 12 months after CAR T-cell infusion, then will be followed per standard of care long-term follow-up until the patient dies, is lost to follow-up, or withdraws consent.
Arms & interventions
- BiologicalVevoctadekin
Given SC
- ProcedureBone Marrow Aspiration
Undergo bone marrow aspiration
- ProcedureBone Marrow Biopsy
Undergo bone marrow biopsy
- ProcedureComputed Tomography
Undergo CT
- ProcedureEchocardiography Test
Undergo ECHO
- ProcedureLeukapheresis
Undergo leukapheresis
- BiologicalLisocabtagene Maraleucel
Given IV
- ProcedureLumbar Puncture
Undergo lumbar puncture
- ProcedureLymphodepletion Therapy
Undergo lymphodepletion chemotherapy
- ProcedureMultigated Acquisition Scan
Undergo MUGA
- ProcedurePositron Emission Tomography
Undergo PET scan
- ProcedureX-Ray Imaging
Undergo x-ray
- ProcedureBiospecimen Collection
Undergo blood and CSF sample collection
Outcome measures
Primary
Incidence of adverse events (AEs)
Will be graded in severity according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, with the exception of cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, which will be graded according to the American Society for Transplantation and Cellular Therapy consensus criteria. The type, frequency, and severity of AEs and laboratory abnormalities will be listed and summarized.
Time frame: Up to 4 years
Dose limiting toxicities (DLT)
Will be graded in severity according to the NCI CTCAE version 5.0. Will be summarized based on the DLT evaluable population. Final DLT rates at each dose level will be estimated by isotonic regression by applying the pooled adjacent violators algorithm. The target toxicity rate is 30%.
Time frame: Up to 21 days following the first vevoctadekin (ST-067) dose
Optimal biological regimen
Will be assessed based on safety and tolerability, confirmation of maximum target engagement, optimal biological effects without undesirable clinical effects, pharmacokinetics parameters, and biological response data.
Time frame: Up to 4 years
Complete response (CR) rate
Will be assessed by Lugano criteria. Will be summarized along with the 2-sided 95% exact Clopper-Pearson confidence interval (CI) based on the efficacy-evaluable population.
Time frame: At 3 months after liso-cel infusion
Secondary
CR rates
Time frame: At 6 months after liso-cel infusion
Overall response rates
Time frame: At 6 months after liso-cel infusion
Duration of response (DOR)
Time frame: Up to 4 years
Progression free survival (PFS)
Time frame: Up to 4 years
Overall survival (OS)
Time frame: Up to 4 years
Eligibility criteria
Study locations (1)
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, 98109